Pteridine derivatives

ABSTRACT

4-substituted-pyrido[3,2-d]pyridmidine, -pyrido[4,3-d]pyrimidine, -pyrido[3,4-d]pyrimidine, pyrido[2,3-d]pyrimidine, -pteridine, -pyrimido[4,5-d]pyrimidine, -pyrimido[4,5-c]pyridazine, -pyrimido[5,4-d]pyrimidine, -pyrimido[5,4-c]pyridazine, pyrimido[4,5-d]pyridazine, and pyrimido[5,4-e]-1,2,4-triazine derivatives, for example 4-[2-(4-chlorophenyl)ethoxy]pyrido[2,3-d]pyrimidine, are useful as fungicides, inseciticides and miticides.

This application is a division of application Ser. No. 07/385,840, filed Jul. 27, 1989 now U.S. Pat. No. 5,034,393.

FIELD OF THE INVENTION

This invention provides new compounds that have excellent plant fungicide activity. Some of the compounds have also demonstrated insecticidal and miticidal activity. The invention also provides compositions and combination products that contain a compound of the invention as active ingredient, as well as providing fungicidal, miticidal, and insecticidal methods.

There is an acute need for new fungicides, insecticides, and miticides, because target pathogens are rapidly developing resistance to currently used pesticides. Widespread failure of N-substituted azole fungicides to control barley mildew was observed in 1983, and has been attributed to the development of resistance. At least 50 species of fungi have developed resistance to the benzimidazole fungicides. The field performance of DMI (demethylation inhibitor) fungicides, which are now widely relied on to protect cereal crops from powdery mildew, has declined since they were introduced in the 1970's. Even recently introduced fungicides, like the acylalanines, which initially exhibited excellent control of potato late blight and grape downy mildew in the field, have become less effective because of widespread resistance. Similarly, mites and insects are developing resistance to the miticides and insecticides in current use. Resistance to insecticides in arthropods is widespread, with at least 400 species resistant to one or more insecticides. The development of resistance to some of the older insecticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pyrethroid insecticides and miticides. Therefore a need exists for new fungicides, insecticides, and miticides.

SUMMARY OF THE INVENTION

This invention provides compounds of the formula (1): ##STR1## wherein one or two of A, B, E, or D are N, and the others are CR¹ or A, E, and D are N and B is CR¹ ; where R¹ and R² are independently H, halo, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, (C₁ -C₄) alkoxy, halo (C₁ -C₄) alkyl, phenyl, or substituted phenyl;

X is O, S, SO, SO₂, NR³, or CR⁴ R⁵, where R³ is H, (C₁ -C₄) alkyl, or (C₁ -C₄) acyl, and R⁴ and R⁵ are independently H, (C₁ -C₄) acyl, (C₁ -C₄) alkyl, (C₂ -C₄) alkenyl or -alkynyl, CN, or OH, or R⁴ and R⁵ combine to form a carbocyclic ring containing four to six carbon atoms;

Y is a bond or an alkylene chain one to six carbon atoms long, optionally including a carbocyclic ring, and optionally including a hetero atom selected from O, NR³, S, SO, SO₂, or SiR²⁰ R²¹, where R³ is as defined above and R²⁰ and R²¹ are independently (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl, or substituted phenyl, and optionally substituted with (C₁ -C₄) alkyl, (C₂ -C₄) alkenyl or- alkynyl, branched (C₃ -C₇) alkyl, (C₃ -C₇) cycloalkyl or -cycloalkenyl, halo, hydroxy, or acetyl, and

Z is

(a) a C₁ -C₁₂ saturated or unsaturated hydrocarbon chain, straight chain or branched optionally including a hetero atom selected from O, S, SO, SO₂, or SiR²⁰ R²¹, where R²⁰ and R²¹ are as defined above and optionally substituted with halo, halo (C₁ -C₄) alkoxy, hydroxy, (C₃ -C₈) cycloalkyl or cycloalkenyl, or (C₁ -C₄) acyl;

(b) (C₃ -C₈) cycloalkyl or cycloalkenyl, optionally substituted with (C₁ -C₄) alkyl, (C₁ -C₄) alkoxy, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, halo, hydroxy, or (C₁ -C₄) acyl;

(c) a phenyl group of the formula (2) ##STR2## where R⁶ to R¹⁰ are independently H, halo, I, (C₁ -C₁₀) alkyl, (C₃ -C₈) alkenyl or -alkynyl, branched (C₃ -C₆) alkyl, -alkenyl, or -alkynyl, (C₃ -C₈) cycloalkyl or -cycloalkenyl, halo (C₁ -C₇) alkyl, (C₁ -C₇) alkoxy, (C₁ -C₇) alkylthio, halo (C₁ -C₇) alkoxy, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, phenyl, substituted phenyl, NO₂, acetoxy, OH, CN, SiR¹¹ R¹² R¹³, OSiR¹¹ R¹² R¹³, NR¹⁴ R¹⁵, S(O)R¹⁶, or SO₂ R¹⁷ where R¹¹, R¹², and R¹³ are independently (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl, or substituted phenyl, R¹⁴ and R¹⁵ are independently H, (C₁ -C₄) alkyl, or (C₁ -C₄) acyl, and R¹⁶ and R¹⁷ are (C₁ -C₁₀) alkyl, phenyl, or substituted phenyl;

(d) a furyl group of formula (3) ##STR3## where R¹⁸ is H, halo, halomethyl, CN, NO₂, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl, or (C₁ -C₄) alkoxy;

(e) a thienyl group of the formula (4) ##STR4## where R¹⁸ is as defined in paragraph (d); (f) a group of formula (5) or (6) ##STR5## where R¹⁸ is as defined in paragraph (d), J is N or CH, and G is O, NR¹⁹, or S, provided that if J is not N then G is NR¹⁹, where R¹⁹ H, (C₁ -C₄) alkyl, (C₁ -C₄) acyl, phenylsulfonyl, or substituted phenylsulfonyl;

(g) a group selected from

optionally substituted naphthyl, dihydronaphthyl, tetrahydronaphthyl, and decahydronaphthyl;

optionally substituted pyridyl;

optionally substituted indolyl;

and 1,3-benzodioxolyl;

or an acid addition salt of a compound of formula (1);

provided that the following compounds are excluded:

1) pyrido[2,3-d]pyrimidines of formula (1) wherein X is NR³ and --Y--Z is benzyl, or X is NR³, Y is an alkylene chain containing an O or S atom adjacent to Z, and Z is either unsubstituted phenyl or a substituted phenyl group other than one substituted with

branched (C₃ -C₆) alkyl,

halo (C₁ -C₄) alkyl,

halo (C₁ -C₄) alkoxy,

phenyl,

substituted phenyl,

phenoxy,

substituted phenoxy,

phenylthio,

substituted phenylthio,

SiR¹¹ R¹² R¹³, or

OSiR¹¹ R¹² R¹³ ;

2) pyrido[3,4-d]pyrimidines of formula (1) wherein X is NR³, Z is unsubstituted phenyl, and R² is methyl; and

3) pyrido[3,4-d]pyrimidines of formula (1) wherein X is NR³ and --Y--Z is benzyl or isoamyl.

Proviso (1) excludes compounds that are described as fungicides in Japanese patent application 5108806 of Sankyo. Proviso (2) excludes compounds for which cytokinin activity is reported in Agri. Biol. Chem., 50, 2243-49 (1986). Proviso (3) excludes compounds for which cytokinin activity is reported in Agri. Biol. Chem., 50, 495-97 (1986).

The fungicide combinations of the invention comprise at least 1% by weight of a compound of formula (1), excluding compounds of proviso (1) but including those of provisos (2) and (3), in combination with a second plant fungicide.

The fungicide compositions of the invention comprise a disease inhibiting and phytologically acceptable amount of compound of formula (1), excluding compounds of proviso (1) but including those of provisos (2) and (3), in combination with a phytologically-acceptable carrier. Such compositions may optionally contain additional active ingredients, such as an additional fungicidal, miticidal, or insecticidal ingredient.

The fungicidal method of the invention comprises applying to the locus of a plant pathogen a disease inhibiting and phytologically acceptable amount of a compound of formula (1), excluding compounds of proviso (1) but including those of provisos (2) and (3).

The insecticide and miticide combinations of the invention comprise at least 1% by weight of a compound of formula (1), including compounds of provisos (1) to (3), in combination with a second insecticide or miticide.

The insecticide and miticide compositions of the invention comprise an insect- or mite-inactivating amount of a compound of formula (1), including compounds of provisos (1) to (3), in combination with a carrier. Such compositions may optionally contain additional active ingredients, such as an additional fungicidal, miticidal, or insecticidal ingredient.

The insecticidal or miticidal method of the invention comprises applying to the locus to be protected an insect- or mite-inactivating amount of a compound of formula (1), including compounds of provisos (1) to (3), or of a combination described above.

DETAILED DESCRIPTION OF THE INVENTION

Throughout this document, all temperatures are given in degrees Celsius, and all percentages are weight percentages unless otherwise stated.

The term "halo" refers to a F, Cl, or Br atom.

The term "(C₁ -C₇) alkoxy" refers to straight or branched chain alkoxy groups.

The term "(C₁ -C₇) alkylthio" refers to straight and branched chain alkylthio groups.

The term "halo (C₁ -C₇) alkyl" refers to a (C₁ -C₇) alkyl group, straight chain or branched, substituted with one or more halo atoms.

The term "halo (C₁ -C₇) alkoxy" refers to a (C₁ -C₇) alkoxy group substituted with one or more halo groups.

The term "halo (C₁ -C₄) alkylthio" refers to a (C₁ -C₄) alkylthio group, straight chain or branched, substituted with one or more halo atoms.

The term "substituted phenyl" refers to phenyl substituted with up to three groups selected from halo, I, (C₁ -C₁₀) alkyl, branched (C₃ -C₆) alkyl, halo (C₁ -C₄) alkyl, hydroxy (C₁ -C₄) alkyl, (C₁ -C₄) alkoxy, halo (C₁ -C₄) alkoxy, phenoxy, substituted phenoxy, phenyl, substituted phenyl, NO₂, OH, CN, (C₁ -C₄) alkanoyloxy, or benzyloxy.

The terms "substituted naphthyl", "substituted pyridyl" and "substituted indolyl" refer to these ring systems substituted with halo, halo (C₁ -C₄) alkyl, CN, NO₂, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl, substituted phenyl, (C₁ -C₄) alkoxy, or halo (C₁ -C₄) alkoxy.

The term "substituted phenoxy" refers to phenoxy substituted with up to three groups selected from halo, I, (C₁ -C₁₀) alkyl, branched (C₃ -C₆) alkyl, halo (C₁ -C₇) alkyl, hydroxy (C₁ -C₇) alkyl, (C₁ -C₇) alkoxy, halo (C₁ -C₇) alkoxy, phenoxy, substituted phenoxy, phenyl, substituted phenyl, NO₂, OH, CN, (C₁ -C₄) alkanoyloxy, or benzyloxy.

The term "carbocyclic ring" refers to a saturated or unsaturated carbocyclic ring containing three to seven carbon atoms.

The terms "substituted phenylthio" and "substituted phenyl sulfonyl" refer to such groups substituted with up to three groups selected from halo, I, (C₁ -C₁₀) alkyl, branched (C₃ -C₆) alkyl, halo (C₁ -C₇) alkyl, hydroxy (C₁ -C₇) alkyl, (C₁ -C₇) alkoxy, halo (C₁ -C₇) alkoxy, phenoxy, substituted phenoxy, phenyl, substituted phenyl, NO₂, OH, CN, (C₁ -C₄) alkanoyloxy, or benzyloxy.

The term "unsaturated hydrocarbon chain" refers to a hydrocarbon chain containing one or two sites of unsaturation.

The term "HPLC" refers to a high-performance liquid chromatography.

Compounds

Compounds of formula (1) wherein A is N and B, E, and D are CR¹ are pyrido [3,2-d]pyrimidines.

Compounds of formula (1) wherein B is N and A, E, and D are CR¹ are pyrido [4,3-d]pyrimidines.

Compounds of formula (1) wherein E is N and A, B, and D are CR¹ are pyrido[3,4-d]pyrimidines.

Compounds of formula (1) wherein D is N and A, B, and E are CR¹ are pyrido[2,3-d]pyrimidines.

Compounds of formula (1) wherein A and D are N and B and E are CR¹ are pteridines (or pyrazino[2,3-d]pyrimidines.

Compounds of formula (1) wherein B and D are N and A and E are CR¹ are pyrimido[4,5-d]pyrimidines.

Compounds of formula (1) wherein E and D are N and A and B are CR¹ are pyrimido[4,5-c]pyridazines.

Compounds of formula (1) wherein A and E are N and B and D are CR¹ are pyrimido[5,4-d]pyrimidines.

Compounds of formula (1) wherein A and B are N and E and D are CR¹ are pyrimido[5,4-c]pyridazines.

Compounds of formula (1) wherein B and E are N and A and D are CR¹ are pyrimido[4,5-d]pyridazines.

Compounds of formula (1) wherein A, E, and D are N and B is CR¹ are pyrimido[5,4-e]-1,2,4-triazines.

While all of the compounds of the invention are useful fungicides, certain classes are preferred for reasons of greater efficacy or ease of synthesis, viz:

(a) compounds of formula (1) wherein one of A, B, E, and D is N and the rest are CR¹.

(b) compounds of class (a) wherein D is N and A, B, and E are CR¹, i.e., pyrido[2,3-d]pyrimidine derivatives;

(c) compounds of formula (1) wherein Z is substituted phenyl;

(d) compounds of formula (1) wherein X is O;

and

(e) compounds of class (d) wherein Y is a chain at least two atoms long.

Synthesis

The compounds of this invention are made using well known chemical procedures. The required starting materials are commercially available, or they are readily synthesized using standard procedures.

Synthesis of Compounds Wherein X is O

The compounds of formula (1) wherein X is O are made by condensing a compound of formula (7): ##STR6## where R², A, B, E, and D are as previously defined, and L is a leaving group such as F, Cl, Br, I, NO₂, 1,2,4-triazol-1-yl, --O--Si(Me)₃, arylthio, alkylthio, alkylsulfonyl, arylsulfonyl, alkoxy, or arylsulfinyl with an alcohol or phenol of the formula (8):

    HO--Y--Z                                                   (8)

where

Y and Z are as previously defined.

For many of the examples, the reaction was carried out in toluene treated with dry HCl, at room temperature or with gentle heating.

Alternatively, and preferably, the reaction may be carried out in the presence of a strong base, such as sodium hydride, in a non-reactive organic solvent, such as DMF, at a temperature in the range of 0° to 25° C.

Synthesis of Compounds Wherein X is NR³

The compounds of formula (1) wherein X is NR³ are prepared by condensing a compound of formula (7) with an amine of the formula (9) ##STR7## where R³ ' is H or (C₁ -C₄) alkyl, and

Y and Z are as previously defined. The chloride of formula (7) is allowed to react with an appropriate amine at a wide variety of temperatures (20°-180° C.), preferably in the presence of an acid acceptor, such as triethylamine. The reaction may be carried out neat, or in a non-reactive organic solvent. Compounds where R³ is acyl are prepared from amines where R³ is H, which were allowed to react with an acylating agent such as acetyl chloride or acetic anhydride. In cases where the starting material of formula (7) is one wherein R¹ or R² is Cl, a mixture of products is obtained which are separable using liquid chromatography.

Synthesis of Compounds Wherein X is CH₂

The compounds of formula (1) wherein X is CH₂ can be made using the process described in J. Heterocyclic Chemistry, Vol. 14, p. 1081-1083 (1977) by A. Scoville and F. X. Smith. This process entails preparation of a barbituric acid of the formula (10) ##STR8## which is then hydrolyzed and decarboxylated by dissolving the intermediate in a solution of sodium hydroxide and water, refluxing, then making the solution slightly acidic with hydrochloric acid and again refluxing.

The acid addition salts of compounds of formula (1) are obtained in the usual way.

Accordingly, the invention also provides a process for preparing a compound of formula (1) which comprises:

(a) condensing a compound of formula (7) ##STR9## wherein R¹, R², A, B, E, and D are as previously defined, and L is a leaving group with an alcohol of the formula (8):

    HO--Y--Z                                                   (8)

wherein Y and Z are as previously defined to produce a compound of formula (1) wherein X is O; or

(b) condensing a compound of formula (7) as defined above with an amine of the formula (9) ##STR10## where R³ ' is H or (C₁ -C₄) alkyl, and Y and Z are as previously defined, to provide a compound of formula (1) where X is NR³ '; or

(c) acylating a compound of formula (1) wherein X is NR³ ' to provide a compound of formula (1) wherein X is NR³ and R³ is acyl; or

(d) hydrolyzing and decarboxylating a compound of formula (10) ##STR11## to produce a compound of formula (1) wherein X is CH₂.

Preparation of Pyridopyrimidine, Pyrimidopyrimidine, and Pteridine Starting Materials

4-Hydroxyridopyrimidine starting materials are commercially available or readily prepared using conventional procedures. For example, useful synthetic procedures are described in

R. K. Robins & G. H. Hitchings, J. Am. Chem. Soc., 77, 2256 (1955);

S. Gabriel & J. Colman, Chem. Ber., 35, 2831 (1902); and

C. C. Price & D. Y. Curtin, J. Am. Chem. Soc., 68, 914 (1946).

4-Hydroxypyrimido[4,5-d]pyrimidines can be prepared using the procedure described in E. C. Taylor, et al., J. Amer. Chem. Soc., 82, 6058 (1960).

4-Hydroxypteridines can be prepared using the procedures described in A. Albert, D. J. Brown and G. Cheesman, J. Chem. Soc., 474 (1951).

4-Hydroxypyrimido[4,5-c]pyridazines can be prepared by the procedures described in J. L. Styles and R. W. Morrison, J. Org. Chem., 50, 346 (1985).

4-Hydroxypyrimido[5,4-d]pyrimidines can be prepared by the procedures described in F. A. Gianturro, P. Gramaccioni, and A. Vaciago, Gazz. Chim. Ital., 99, 1042 (1969).

4-Hydroxypyrimido[5,4-c]pyridazines can be prepared by the procedures described in R. N. Castle and H. Murakami, J. Hetero. Chem., 5, 523 (1968).

4-Hydroxypyrimido[4,5-d]pyridazines can be prepared by the procedures described in R. N. Castle, J. Hetero. Chem., 5, 845 (1968).

4-Chloro derivatives of formula (7) wherein L is Cl are prepared by chlorodehydroxylation of the corresponding 4-keto compounds using conventional methods, for example by reaction with POCl₃.

Intermediates of formula (7) wherein L is 1,2,4-triazol 1-yl, can be prepared, for example, by adding POCl₃ dropwise to a mixture of a 4-hydroxypyridopyrimidine (1 equiv.) and 1,2,4-triazole (3 equiv.) in pyridine at a temperature from 20° to 100° C.

EXAMPLES 1-72

The following examples are compounds actually prepared by the above described general procedures. The melting point is given for each compound. In addition, although the data has not been included, each compound was fully characterized by NMR, IR, mass spectra, and combustion analysis. Specific illustrative preparations for the compounds of Examples follow the tabular listing.

    ______________________________________                                         EXAMPLE                                                                        NUMBER   COMPOUND              M.P.                                            ______________________________________                                          1       4-(4-fluorophenoxy)pyrido[2,3-d]-                                                                    142-144° C.                                       pyrimidine                                                             2       4-[2-[4-( .sub.. i-propyl)phenyl]ethyl-                                                              198-200° C.                                       amino]pyrido[2,3-d]pyrimidine                                          3       4-[2-(4-chlorophenyl)ethoxy]pyrido-                                                                  126-128° C.                                       [2,3-d]pyrimidine                                                      4       4-[2-(4-chlorophenyl)ethoxy]pyrido-                                                                  86° C.                                            [3,2-d]pyrimidine                                                      5       4-[2-[4-( .sub.- t-butyl)phenyl]ethylamino]-                                                         77-78° C.                                         pyrido[3,2-d]pyrimidine                                                6       4-(2-chloro-4-fluorophenoxy)pyrido-                                                                  181-182° C.                                       [2,3-d]pyrimidine                                                      7       4-[2-(4-ethoxyphenyl)ethoxy]pyrido-                                                                  74-75° C.                                         [3,2-d]pyrimidine                                                      8       N-(2-phenylethyl)pyrido[2,3-d]-                                                                      252-254° C.                                       pyrimidin-4-amine                                                      9       N-[2-(2-naphthalenyl)ethyl]pyrido-                                                                   247-251° C.                                       [2,3-d]pyrimidin-4-amine                                              10       4-[2-(2,4-difluorophenyl)ethoxy]-                                                                    84-85° C.                                         pyrido[2,3-d]pyrimidine                                               11       4-[2-(4-ethoxylphenyl)ethoxy]pyrido-                                                                 62-64° C.                                         [2,3-d]pyrimidine                                                     12       N-[2-[3-(trifluoromethyl)phenyl]-                                                                    190-193° C.                                       ethyl]pyrido[2,3-d]pyrimidin-4-amine                                  13       N-(4-phenylbutyl)pyrido[2,3-d]-                                                                      179-181° C.                                       pyrimidin-4-amine                                                     14       N-(3-phenylpropyl)pyrido[2,3-d]-                                                                     195-198° C.                                       pyrimidin-4-amine                                                     15       4-(2-phenylethoxy)pyrido[2,3-d]-                                                                     101-102° C.                                       pyrimidine                                                            16       N-[2-(4-chlorophenyl)ethyl]pyrido-                                                                   271-275° C.                                       [2,3-d]pyrimidin-4-amine                                              17       4-[2-(4-methoxy-3-methylphenyl)-                                                                     113-114° C.                                       ethoxy]pyrido[2,3-d]pyrimidine                                        18       4-[3-(4-phenoxyphenyl)propoxy]-                                                                      oil                                                      pyrido[2,3-d]pyrimidine                                               19       N-[(4-chlorophenyl)methyl]pyrido-                                                                    252-255° C.                                       [2,3-d]pyrimidin-4-amine                                              20       N-[2-(2,6-difluorophenyl)ethyl]-                                                                     263-266° C.                                       pyrido[2,3-d]pyrimidin-4-amine                                        21       4-[2-[4-(trimethylsilyl)phenyl]-                                                                      90° C.                                           ethoxy]pyrido[2,3-d]pyrimidine                                        22       4-[2-(2-naphthalenyl)ethoxy]pyrido-                                                                  108° C.                                           [2,3-d]pyrimidine                                                     23       4-[2-(4-methoxyphenyl)ethoxy]-                                                                       109-110° C.                                       pyrido[2,3-d]pyrimidine                                               24       4-(4-fluorophenoxy)pyrido[3,4-d]-                                                                    212-214° C.                                       pyrimidine                                                            25       4-[2-[4-phenylphenyl]ethoxy]pyrido-                                                                  124-125° C.                                       [2,3-d]pyrimidine                                                     26       4-[2-[4-( .sub.- t-butyl)phenyl]ethoxy]-                                                             59-60° C.                                         pyrido[3,-d]pyrimidine                                                27       4-[2-[4-(t-butyl)phenyl]-ethyl-                                                                      209-211° C.                                       amino]pyrido[2,3-d]pyrimidine                                         28       4-[2-[4-( .sub.- i-propyl)phenyl]ethyl-                                                              165-167° C.                                       amino]pyrido[3,4-d]pyrimidine                                         29       4-[2-[4-( .sub.- t-butyl)phenyl]ethoxy]-                                                              55° C.                                           pyrido[3,2-d] pyrimidine                                              30       4-[2-[4-(trifluoromethyl)phenyl]-                                                                    65-67° C.                                         ethoxy]pyrido[2,3-d]pyrimidine                                        31       4-(4-fluorophenoxy)pyrido[3,2-d]-                                                                    149-151° C.                                       pyrimidine                                                            32       4-[2-[4-(trimethylsilyl)phenyl]-                                                                      81° C.                                           ethoxy]pyrido[3,4-d]pyrimidine                                        33       4-[2-(4-ethoxyphenyl)ethoxy]pyrido-                                                                  87-88° C.                                         [3,4-d]pyrimidine                                                     34       N-[2-(4-methoxyphenyl)ethyl]-                                                                        260-263° C.                                       pyrido[2,3-d]pyrimidin-4-amine                                        35       N-[2-(4-methoxyphenyl)ethyl]-                                                                        153-155° C.                                       pyrido[3,4-d]pyrimidin-4-amine                                        36       4-(2-[1,1'-biphenyl]-4-ylethoxy)-                                                                    137-138° C.                                       pyrido[3,4-d]pyrimidine                                               37       N-[2-[4-( .sub.- t-butyl)phenyl]ethyl]-                                                              138-163° C.                                       pyrido[3,4-d]pyrimidin-4-amine                                        38       N-[2-(4-ethoxyphenyl)ethyl]-                                                                         174-176° C.                                       pyrido[3,4-d]pyrimidin-4-amine                                        39       N-(4-phenylbutyl)pyrido[3,4-]-                                                                       60-75° C.                                         pyrimidin-4-amine                                                     40       N-[2-(4-ethoxyphenyl)ethyl]pyrido-                                                                   220-222° C.                                       [2,3-d]pyrimidin-4-amine                                              41       4-[2-[4-( .sub.- t-butyl)phenyl]ethoxy]-                                                             77-79° C.                                         pyrido[2,3-d]pyrimidine                                               42       N-[[3-trifluoromethyl)phenyl]-                                                                       202-201° C.                                       methyl]pyrido[2,3-d]pyrimidin-4-                                               amine                                                                 43       N-[[4-(trifluoromethoxy)phenyl]-                                                                     247-249° C.                                       methyl]pyrido[2,3-d]pyrimidin-4-                                               amine                                                                 44       N-[2-(4-methylphenyl)ethyl]pyrido-                                                                   260-264°  C.                                      [2,3-d]pyrimidin-4-amine                                              45       N-[2-(2-methoxyphenyl)ethyl]pyrido-                                                                  158-171° C.                                       [2,3-d]pyrimidin-4-amine                                              46       N-(2-phenylethyl)pyrido[3,4-d]-                                                                      134-137° C.                                       pyrimidin-4-amine                                                     47       N-[4-(trifluoromethyl)phenyl]pyrido-                                                                 283-290° C.                                       [2,3-d]pyrimidin-4-amine                                              48       4-[[2-(4-methoxyphenyl)ethyl]amino]-                                                                 120-122° C.                                       pyrido[3,2-d]pyrimidine                                               49       N-(2-phenylethyl)pyrido[3,2-d]pyri-                                                                  135-137° C.                                       midin-4-amine                                                         50       N-[2-[4-( .sub.- t-butyl)phenyl]ethyl]-                                                              157-158° C.                                       pyrido-[4,3-d]pyrimidin-4-amine                                       51       N-[2-(2-naphthyl)ethyl]pyrido-                                                                       140-143° C.                                       [3,2-d]pyrimidin-4-amine                                              52       N-methyl-N-(2-phenylethyl)pyrido-                                                                    114-116° C.                                       [2,3-d]pyrimidin-4-amine                                              53       N-methyl-N-[phenylmethyl)pyrido-                                                                      99-101° C.                                       [2,3-d]pyrimidin-4-amine                                              54       4-[2-(4-methylphenyl)ethoxy]-                                                                        91-92° C.                                         pyrido[2,3-d]pyrimidine                                               55       4-[2-[4-( .sub.- t-butyl)phenyl]ethoxy]-                                                             149° C.                                           pteridine                                                             56       4-[2-(4-methylphenyl)ethoxy]pyrido-                                                                  74-75° C.                                         [3,4-d]pyrimidine                                                     57       4-[2-(biphenyl)ethoxy]pyrido[3,2-d]-                                                                 83-84° C.                                         pyrimidine                                                            58       4-[2-(4-methoxyphenyl)ethoxy]pyrido-                                                                 80-81° C.                                         [3,4-d]pyrimidine                                                     59       4-[(4-methylphenyl)methoxy]pyrido-                                                                   110-111° C.                                       [2,3-d]pyrimidine                                                     60       4-(2-cyclohexylethoxy)pyrido[2,3-d]-                                                                  72° C.                                           pyrimidine                                                            61       4-[2-(phenyl)ethoxy]pyrido[3,4-d]-                                                                   77-78° C.                                         pyrimidine                                                            62       4-[2-(4-chlorophenyl)ethoxy]pyrido-                                                                  108-109° C.                                       [3,4-d]pyrimidine                                                     63       4-(3-phenylpropoxy)pyrido[2,3-d]-                                                                    34-36° C.                                         pyrimidine                                                            64       4-[(2-phenylethyl)amino]pteridine                                                                    159-160° C.                              65       N-[2-(4-ethylphenyl)ethyl]pyrido-                                                                    218-220° C.                                       [2,3-d]pyrimidin-4-amine                                              66       N-(2-ethoxyethyl)pyrido[2,3-d]-                                                                      N.A.                                                     pyrimidin-4-amine                                                     67       N-(2-methoxyethyl)pyrido[2,3-d]-                                                                     190-193° C.                                       pyrimidin-4-amine                                                     68       N-[2-(2-chloro-6-fluorophenyl)-                                                                      248-251° C.                                       ethyl]pyrido[2,3-d]pyrimidin-4-amine                                  69       N-[3-(diethylamino)propyl]pyrido-                                                                    163-167° C.                                       [2,3.d]pyrimidin-4-amine                                              70       N-[2-[4-( .sub.- t-butyl)phenyl]ethyl]-4-                                                            147° C.                                           pteridinamine                                                         71       N-(phenylmethyl)pyrido[2,3-d]-                                                                       258-260° C.                                       pyrimidin-4-amine                                                     72       4-[2-(2-methyl)ethoxy]pyrido-                                                                        128-129° C.                                       [3,4-d]pyrimidine                                                     ______________________________________                                    

The procedures described in the following detailed examples are representative of the procedures used to prepare the compounds of the other examples.

Preparation 1 Pyrido[34-d]pyrimidin-4(3H)one

A mixture of 4 g of 3-amino-pyridine-4-carboxylic acid in 15 mL of formamide was heated in an oil bath to 160°-180° C. After one hour the mixture was allowed to cool. Then, the mixture was slurried in 25 mL of water and filtered. The product was recrystallized from water. Yield 3.3 g. M.P. 317° C. (with sublimation).

Preparation 2 Pyrido[3,2-d]pyrimidin-4(3H)one

A mixture of 6.5 g of 3-amino-pyridine-2-carboxylic acid in 9 g of formamide was heated in an oil bath while stirring. The temperature was increased from 130° C. to 180° C. over a two hour period, then the mixture was allowed to cool. The mixture was then diluted with water. The solids were collected and washed with fresh water, then dried. Yield 4.6 g. M.P. 346°-347° C.

Preparation 3 4-Chloropyrido[2,3-d]pyrimidine

A mixture of 17.8 g of Pyrido[2,3-d]pyrimidin(4(3H)one and 200 mL of POCl₃ was stirred under reflux for one hour. Excess POCl₃ was removed under vacuum, and then CH₂ Cl₂, ice, and water were added. A black solid dissolved slowly. The organic layer was then separated, washed with aqueous NaHCO₃, and dried over Na₂ SO₄. Solvent was then removed under vacuum to leave a yellow solid, which was recrystallized from toluene/hexane. M.P. 137° dec.

Preparation 4 4-[1'-(1,2,4-triazolyl)]pyrido[2,3-d]-pyrimidine

A. A mixture of 28.5 g of Pyrido[2,3-d]-pyrimidin-4(3H)one and 40.1 g of 1,2,4-triazole in 500 mL of pyridine was stirred as 71.4 g of 4-chlorophenyl dichlorophosphate was added with modest cooling. The mixture was then stirred at room temperature. Then 2.5 L of CH₂ Cl₂ was added, and the mixture was washed successively with 500 mL of water, 1 L of 2% HCl, and 500 mL of water, then dried over MgSO₄. Solvent was then evaporated, leaving a yellow solid, which was recrystallized from toluene/hexane to give 9.0 g first crop, M.P. 206°-210° C., 5.7 g second crop, M.P. 218°-220° C., 1.45 g third crop, M.P. 205°-209° C.

B. The title compound was also made by mixing 1.47 g of pyrido[2,3-d]pyrimidin-4(3H)one and 2.07 g of 1,2,4-triazole in 50 mL of pyridine and adding 1.12 mL of POCl₃ while stirring the mixture at room temperature. After stirring the mixture overnight, 500 mL of CH₂ Cl₂ was added, and the mixture was washed successively with 500 mL of 2% HCl and 500 mL of water, and then dried over MgSO₄. Solvent was evaporated under vacuum to leave 0.4 of yellow solid, which was recrystallized from toluene/hexane. M.P. 217°-219° C.

Example 2 4-[2-[4-(i-propyl )phenyl]ethylamino]pyrido[2,3-d]pyrimidine

A mixture consisting of 1.98 g (0.01 mole) of 4-[1'-(1,2,4-triazolyl)]pyrido[2,3-d]pyrimidine, 1.63 g (0.01 mole) of 2-[4-(i-propyl)phenyl]ethylamine, and 50 mL of CHCl₃ was stirred at reflux for two hours. Then 1.01 g (0.01 mole) of triethyl amine was added, and the mixture was refluxed for four hours. After washing the mixture with water, the CHCl₃ layer was dried over MgSO₄. The CHCl₃ was removed using a vacuum and the product was recrystallized from EtOH/H₂ O. Yield 1.5 g. This product was recrystallized from ethyl acetate. M.P. 200°-203° C.

Example 3 4-[2-(4-chlorophenyl)ethoxy]pyrido[2,3-d]pyrimidine

A mixture consisting of 1.48 g (7.5 mmole) of 4-[1'-(1,2,4-triazolyl)-pyrido[2,3-d]pyrimidine, 1.20 g of 2-(4-chlorophenyl)ethanol (7.5 mmole), and 50 mL of toluene which had been treated with dry HCl gas was stirred at room temperature, heated gently for about one and one half hours, then cooled. TLC indicated that the reaction was not complete, so additional alcohol was added and the mixture was warmed. After cooling the mixture, it was diluted with water and made basic with 1.0N NaOH. The product was extracted from the mixture into toluene, which was then washed with saturated brine, filtered through phase separating paper, and concentrated in vacuo. The oily residue that crystallized was chromatographed (silica gel, CH₂ Cl₂ →70% CH₂ Cl₂ /30% EtOAc). The fractions containing the major product were combined, and the product crystallized. The product was recrystallized from CH₂ Cl₂ /petroleum ether. Yield 1.05 g. M.P. 126°-128° C.

Example 26 4-[ 2-[4-(t-butyl)phenyl]ethoxy]pyrido[3,4-d]pyrimidine

To a suspension of 300 mg of 60% NaH in 15 mL of DMF was added 1.33 g of 2-[4-(t-butyl)phenyl]ethanol. The mixture was stirred at room temperature for 30 minutes. The 1.48 g of 4-[1'-(1,2,4-triazolyl)pyrido[3,4-d]pyrimidine was added and the mixture was stirred at room temperature overnight. Solvent was then removed in vacuo, azeotroping with xylene. The residue was diluted with water and the pH was adjusted to neutral by adding dilute HCl. The product was extracted into CH₂ Cl₂, which was then washed with brine, dried over Na₂ SO₄, filtered, and concentrated. The residue was adsorbed onto silica gel and chromatographed, eluting with CH₂ Cl₂ to 75/25 CH₂ Cl₂ /EtOAc. Fractions containing the major product were combined to give a thick oil which crystallized from petroleum ether. Yield 1.4 g. M.P. 59°-60° C.

Example 41 4-[2-[4-(t-butyl)phenyl]ethoxy]pyrido[2,3-d]pyrimidine

A mixture consisting of 1.86 g (0.011 mole) of 4-chloropyrido-[2,3-d]pyrimidine, 2.0 g (0.011 mole) of 2-[4-(t-butyl)phenyl]ethanol, and 40 mL of toluene containing a little HCl gas was stirred at room temperature. The mixture was then cooled, and a yellow solid was collected. This was washed with hexane, then partitioned between 1N NaOH and CH₂ Cl₂. The CH₂ Cl₂ layer was dried over MgSO₄, then the solvent was removed under vacuum to leave a yellow solid, which was recrystallized from hexane. Yield 2.5 g. M.P. 77°-79° C.

Example 50 4-[2-[4-(t-butyl)phenyl]ethylamino]pyrido[4,3-d]pyrimidine

A mixture consisting of 0.45 g of pyrido[4,3-d]pyrimidine-4-ol, 0.53 g of 2-[4-(t-butyl)phenyl]ethylamine, about 40 mg of (NH₄)₂ SO₄ in 4 mL of hexamethyldisilazane was refluxed for about five hours. The mixture was then cooled and excess disilazane was removed in vacuo. The residue was dissolved in CH₂ Cl₂, and the solution was washed with water and filtered through phase separating paper. Evaporated the CH₂ Cl₂ and adsorbed the residue onto silica gel, which was applied to a thin silica pad and eluted with CH₂ Cl₂ →50% EtOAc/50% CH₂ Cl₂ →EtOAc. Fractions containing the major product were combined and the product which crystallized was recrystallized from hexane/EtOAc. Yield 0.2 g. M.P. 157°-158° C.

Example 55 4-[2-[4-(t-butyl)phenyl]ethoxy]pteridine

To a suspension of 2 g of 4-hydroxypteridine in 20 mL of CH₂ Cl₂ under nitrogen was added 1.2 g of pyridine. The mixture was cooled to -30° C. and over a 15 minute period a solution of 4.82 g of triphenyl phosphite in CH₂ Cl₂ was added simultaneously with addition of chlorine gas. The mixture was stirred for one and one half hours while maintaining the temperature at -15° to -20° C. The mixture was then allowed to warm to 10° C., and a solution of 2.67 g of 2-[4-(t-butyl)phenyl]ethanol in CH₂ Cl₂ was added. The resulting mixture was refluxed for 45 minutes, then cooled and diluted into toluene. The toluene solution was washed with dilute base, then filtered through phase separating paper and concentrated in vacuo. The resulting bluish oil was adsorbed onto silica gel and chromatographed (silica gel, CH₂ Cl₂ →80% CH₂ Cl₂, 20% EtOAc). Fractions containing the major product were combined. The product was then recrystallized from petroleum ether/CH₂ Cl₂. Yield 60 mg. M.P. 149° C.

Fungicide Utility

The compounds of the present invention have been found to control fungi, particularly plant pathogens. When employed in the treatment of plant fungal diseases, the compounds are applied to the plants in a disease inhibiting and phytologically acceptable amount. The term "disease inhibiting and phytologically acceptable amount," as used herein, refers to an amount of a compound of the invention which kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 1 to 1000 ppm, with 10 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type formulation employed, the method of application, the particular plant species, climate conditions and the like. A suitable application rate is typically in the range from 0.25 to 4 lb/A. The compounds of the invention may also be used to protect stored grain and other non-plant loci from fungal infestation.

Greenhouse Tests

The following experiments were performed in the laboratory to determine the fungicidal efficacy of the compounds of the invention.

This screen was used to evaluate the efficacy of the present compounds against a variety of different organisms that cause plant diseases.

The test compounds were formulated for application by dissolving 50 mg of the compound into 1.25 ml of solvent. The solvent was prepared by mixing 50 ml of "Tween 20" (polyoxyethylene (20) sorbitan monolaurate emulsifier) with 475 ml of acetone and 475 ml of ethanol. The solvent/compound solution was diluted to 125 ml with deionized water. The resulting formulation contains 400 ppm test chemical. Lower concentrations were obtained by serial dilution with the solvent-surfactant mixture.

The formulated test compounds were applied by foliar spray. The following plant pathogens and their corresponding plants were employed.

    ______________________________________                                                        Designation in                                                  Pathogen       Following Table                                                                              Host                                              ______________________________________                                         Erysiphe graminis tritici                                                                     POWD          wheat                                             (powdery mildew)                                                                              MDEW                                                            Pyricularia oryzae                                                                            RICE          rice                                              (rice blast)   BLAS                                                            Puccinia recondita tritici                                                                    LEAF          wheat                                             (leaf rust)    RUST                                                            Botrytis cinerea                                                                              GRAY          grape berries                                     (gray mold)    MOLD                                                            Pseudoperonospora cubensis                                                                    DOWN          squash                                            (downy mildew) MDEW                                                            Cercospora beticola                                                                           LEAF          sugar beet                                        (leaf spot)    SPOT                                                            Venturia inaequalis                                                                           APPL          apple seedling                                    (apple scab)   SCAB                                                            Septoria tritici                                                                              LEAF          wheat                                             (leaf blotch)  BLOT                                                            ______________________________________                                    

The formulated technical compounds were sprayed on all foliar surfaces of the host plants (or cut berry) to past run-off. Single pots of each host plant were placed on raised, revolving pedestals in a fume hood. Test solutions were sprayed on all foliar surfaces. ALL treatments were allowed to dry and the plants were inoculated with the appropriate pathogens within 2-4 hours.

The following Table presents the activity of typical compounds of the present invention when evaluated in this experiment. The effectiveness of test compounds in controlling disease was rated using the following scale.

    ______________________________________                                         0          = not tested against specific organism                                         = 0-19% control at 400 ppm                                          +          = 20-89% control at 400 ppm                                         ++         = 90-100% control at 400 ppm                                        +++        = 90-100% control at 100 ppm                                        ______________________________________                                    

    ______________________________________                                         PLANT PATHOLOGY SCREEN                                                         EXAMPLE  POWD     RICE     LEAF  GRAY   DOWN                                   NUMBER   MDEW     BLAST    RUST  MOLD   MDEW                                   ______________________________________                                          1       -        -        -     -      -                                       2       -        -        +++   -      +++                                     3       +        +++      +++   -      +++                                     4       -        ++       +     -      +                                       5       +++      +++      +++   +      +++                                     6       +        -        -     -      +                                       7       +        -        ++    -      +++                                     8       -        -        +++   -      +++                                     9       -        -        ++    -      +                                      10       ++       -        +++   -      +++                                    11       ++       -        +++   -      +++                                    12       -        -        ++    -      +++                                    13       -        -        +++   -      +++                                    14       -        -        +     -      +++                                    15       +        -        +++   -      +++                                    16       -        -        +     -      -                                      17       +++      +++      +++   -      +++                                    18       -        ++       +++   -      +++                                    19       -        -        +     -      -                                      20       -        -        -     -      +                                      21       +++      -        +++   -      +++                                    22       +++      -        +++   -      +++                                    23       -        +++      +++   -      +++                                    24       -        -        -     -      -                                      25       +++      +++      +++   -      +++                                    26       +++      +++      +++   -      +++                                    27       -        +        +++   -      +++                                    28       +++      +++      +++   -      +++                                    29       ++       ++       ++    -      +++                                    30       +++      +++      +++   -      +++                                    31       -        -        -     -      -                                      32       ++       ++       ++    -      ++                                     33       ++       -        ++    -      ++                                     34       -        +        ++    -      ++                                     35       ++       +++      +++   -      +++                                    36       -        ++       +     -      +++                                    37       ++       +++      +++   -      +++                                    38       ++       ++       +++   -      +++                                    39       +++      ++       +++   -      +++                                    40       +        +        +++   -      ++                                     41       +++      +++      +++   -      +++                                    43       -        -        ++    -      +                                      44       -        -        +     -      ++                                     45       -        -        ++    -      ++                                     46       ++       -        ++    -      ++                                     47       -        -        -     -      ++                                     48       ++       ++       ++    -      ++                                     49       +        -        ++    -      ++                                     50       -        -        ++    -      ++                                     51       +++      +        +++   -      +++                                    52       ++       -        ++    -      ++                                     53       -        -        +     0      +                                      54       ++       -        ++    0      ++                                     55       -        -        +     -      +++                                    61       ++       ++       ++    -      ++                                     65       -        -        +++   -      +++                                    67       -        -        -     0      ++                                     72       +        ++       +++   -      +++                                    ______________________________________                                    

Combinations

Fungal disease pathogens are known to develop resistance to fungicides. When strains resistant to a fungicide do develop, it becomes necessary to apply larger and larger amounts of the fungicide to obtain desired results. To retard the development of resistance to new fungicides, it is desirable to apply the new fungicides in combination with other fungicides. Use of a combination product also permits the product's spectrum of activity to be adjusted.

Accordingly, another aspect of the invention is a fungicidal combination comprising at least 1% by weight of a compound of formula (1) in combination with a second fungicide.

Contemplated classes of fungicides from which the second fungicide may be selected include:

1) N-substituted azoles, for example propiconazole, triademefon, flusilazol, diniconazole, ethyltrianol, myclobutanil, and prochloraz;

2) pyrimidines, such as fenarimol and nuarimol;

3) morpholines, such as fenpropimorph and tridemorph;

4) piperazines, such as triforine; and

5) pyridines, such as pyrifenox. Fungicides in these five classes all function by inhibiting sterol biosynthesis. Additional classes of contemplated fungicides, which have other mechanisms of action include:

6) dithiocarbamates, such as maneb and mancozeb;

7) phthalimides, such as captafol;

8) isophthalonitrites, such as chlorothalonil;

9) dicarboximides, such as iprodione;

10) benzimidazoles, such as benomyl and carbendazim;

11) 2-aminopyrimidines, such as ethirimol;

12) carboxamides, such as carboxin;

13) dinitrophenols, such as dinocap; and

14) acylalanines, such as metalaxyl.

The fungicide combinations of the invention contain at least 1%, ordinarily 20 to 80%, and more typically 50 to 75% by weight of a compound of formula (1).

Insecticide and Miticide Utility

The compounds of the invention are also useful for the control of insects and mites. Therefore, the present invention also is directed to a method for inhibiting an insect or mite which comprises applying to a locus of the insect or mite an insect- or mite-inhibiting amount of a compound of formula (1).

The compounds of the invention show activity against a number of insects and mites. More specifically, the compounds show activity against melon aphid, which is a member of the insect order Homoptera. Other members of the Homoptera include leafhoppers, planthoppers, pear pyslla, apple sucker, scale insects, whiteflies, spittle bugs as well as numerous other host specific aphid species. Activity has also been observed against greenhouse thrips, which are members of the order Thysanoptera. The compounds also show activity against Southern armyworm, which is a member of the insect order Lepidoptera. Other typical members of this order are codling moth, cutworm, clothes moth, Indianmeal moth, leaf rollers, corn earworm, European corn borer, cabbage worm, cabbage looper, cotton bollworm, bagworm, eastern tent caterpillar, sod webworm, and fall armyworm.

Representative mite species with which it is contemplated that the present invention can be practiced include those listed below.

    __________________________________________________________________________     FAMILY     SCIENTIFIC NAME                                                                               COMMON NAME                                          __________________________________________________________________________     ACARIDAE                                                                                  Aleurobius farinae                                                             Rhizoglyphus echinopus                                                                        Bulb mite                                                       Rhizoglyphus elongatus                                                         Rhizoglyphus rhizophagus                                                       Rhizoglyphus sagittatae                                                        Rhizoglyphus tarsalis                                               ERIOPHYIDAE                                                                               Abacarus farinae                                                                              Grain rust mite                                                 Aceria brachytarsus                                                            Acalitus essigi                                                                               Redberry mite                                                   Acera ficus                                                                    Aceria fraaxinivorus                                                           Aceria granati                                                                 Aceria parapopuli                                                              Eriophyes sheldoni                                                                            Citrus bud mite                                                 Aceria tulipae                                                                 Aculus carnutus                                                                               Peach silver mite                                               Aculus schlechtendali                                                                         Apple rust mite                                                 Colomerus vitis                                                                               Grape erineum mite                                              Eriophyes convolvens                                                           Eriophyes insidiosus                                                           Eriophyes malifoliae                                                           Eriophyes padi                                                                 Eriophyes pruni                                                                Epitrimerus pyri                                                                              Pear leaf blister mite                                          Eriophyes ramosus                                                              Eriophyes sheldoni                                                                            Citrus bud mite                                                 Eriophyes ribis                                                                Phyllocoptes gracilis                                                                         Dryberry mite                                                   Phyllocoptruta oleivora                                                                       Citrus rust mite                                                Phytoptus ribis                                                                Trisetacus pini                                                                Vasates amygdalina                                                             Vasates eurynotus                                                              Vasates quadripedes                                                                           Maple bladdergall mite                                          Vasates schlechtendali                                              EUPODIDAE                                                                                 Pentaleus major                                                                               Winter grain mite                                               Linopodes spp.                                                      NALEPELLIDAE                                                                              Phylocoptella avellanae                                                                       Filbert bud mite                                     PENTHALEIDAE                                                                              Halotydeus destrustor                                               PYEMOTIDAE                                                                                Pyemotes tritici                                                                              Straw itch mite                                                 Siteroptes cerealium                                                TARSONEMIDAE                                                                              Polyphagotarsonemus latus                                                                     Broad mite                                                      Steneotarsonemus pallidus                                                                     Cyclamen mite                                        TENUIPALPIDAE                                                                             Brevipalpus californicus                                                       Brevipalpus obovatus                                                                          Privet mite                                                     Brevipalpus lewisi                                                                            Citrus flat mite                                                Dolichotetranychus floridanus                                                                 Pineapple flase spider                                                         mite                                                            Tenuipalpes granati                                                            Tenuipalpes pacificus                                               TETRANYCHIDAE                                                                             Bryobia arborea                                                                Bryobia practiosa                                                                             Clover mite                                                     Bryobia rubrioculus                                                                           Brown mite                                                      Eotetranychus coryli                                                           Eotetranychus hicoriae                                                                        Pecan deaf scorch mite                                          Eotetranychus lewisi                                                           Eotetranychus sexmaculatus                                                                    Sixspotted spider mite                                          Eotetranychus willametti                                                       Eotetranychus banksi                                                                          Texas citrus mite                                               Oligonychus ilicis                                                                            Southern red mite                                               Oligonychus pratensis                                                                         Banks grass mite                                                Oligonychus ununguis                                                                          Spruce spider mite                                              Panonychus citri                                                                              Citrus red mite                                                 Panonychus ulmi                                                                               European red mite                                               Paratetranychus modestus                                                       Paratetranychus pratensis                                                      Paratetranychus viridis                                                        Petrobia latens                                                                               Brown wheat mite                                                Schizotetranychus celarius                                                                    Bamboo spider mite                                              Schizotetranychus pratensis                                                    Tetranychus canadensis                                                                        Fourspotted spider mite                                         Tetranychus cinnabarinus                                                                      Carmine spider mite                                             Tetranychus mcdanieli                                                                         McDaniel spider mite                                            Tetranychus pacificus                                                                         Pacific spider mite                                             Tetranychus schoenei                                                                          Schoene spider mite                                             Tetranychus urticae                                                                           Twospotted spider mite                                          Tetranychus turkestani                                                                        Strawberry spider mite                                          Tetranychus desertorum                                                                        Desert spider mite                                   __________________________________________________________________________

The compounds are useful for reducing populations of insects and mites, and are used in a method of inhibiting an insect or mite population which comprises applying to a locus of the insect or arachnid an effective insect- or mite-inactivating amount of a compound of formula (1). The "locus" of insects or mites is a term used herein to refer to the environment in which the insects or mites live or where their eggs are present, including the air surrounding them, the food they eat, or objects which they contact. For example, plant-ingesting insects or mites can be controlled by applying the active compound to plant parts, which the insects or mites eat, particularly the foliage. It is contemplated that the compounds might also be useful to protect textiles, paper, stored grain, or seeds by applying an active compound to such substance. The term "inhibiting an insect or mite" refers to a decrease in the numbers of living insects or mites; or a decrease in the number of viable insect or mite eggs. The extent of reduction accomplished by a compound depends, of course, upon the application rate of the compound, the particular compound used, and the target insect or mite species. At least an insect-inactivating or mite-inactivating amount should be used. The terms "insect-inactivating amount" and "mite-inactivating amount" are used to describe the amount, which is sufficient to cause a measurable reduction in the treated insect or mite population. Generally an amount in the range from about 1 to about 1000 ppm active compound is used.

In a preferred embodiment, the present invention is directed to a method for inhibiting a mite which comprises applying to a plant an effective mite-inactivating amount of a compound of formula (1) in accordance with the present invention.

Mite/Insect Screen

The compounds of Examples 1-10 were tested for miticidal and insecticidal activity in the following mite/insect screen.

Each test compound was formulated by dissolving the compound in acetone/alcohol (50:50) mixture containing 23 g of "TOXIMUL R" (sulfonate/nonionic emulsifier blend) and 13 g of "TOXIMUL S" (sulfonate/nonionic emulsifier blend) per liter. These mixtures were then diluted with water to give the indicated concentrations.

Twospotted spider mites (Tetranychus urticae Koch) and melon aphids (Aphis gossypii Glover) were introduced on squash cotyledons and allowed to establish on both leaf surfaces. Other plants in the same treatment pot were left uninfested. The leaves were then sprayed with 5 ml of test solution using a DeVilbiss atomizing sprayer at 10 psi. Both surfaces of the leaves were covered until runoff, and then allowed to dry for one hour. Two uninfested leaves were then excised and placed into a Petri dish containing larval southern armyworm (Spodopetra eridania Cramer).

Activity on Southern corn rootworm (Diabrotica undecimpuctata howardi Barber) was evaluated by adding two ml of tap water, a presoaked corn seed, and 15 g of dry sandy soil to a one ounce plastic container. The soil was treated with 1 mL of test solution containing a predetermined concentration of test compound. After six to 12 hours of drying, five 2-3 instar corn rootworm larvae were added to the individual cups, which were then capped and held at 23° C.

After standard exposure periods, percent mortality and phytotoxicity were evaluated. Results for the compounds found to be active are reported in the following table. The remaining compounds showed no activity. The following abbreviations are used in the following table:

CRW refers to corn rootworm

SAW refers to Southern armyworm

SM refers to twospotted spider mites

MA refers to melon aphids.

    ______________________________________                                         MITE AND INSECT SCREEN                                                                           SAW       SM       MA                                        EXAMPLE  RATE     RESULTS   RESULTS  RESULTS                                   NUMBER   PPM      %         %        %                                         ______________________________________                                         1        400      0         0        0                                         2        200      0         0        0                                                  400      80        0        0                                         3        200      0         0        0                                                  400      0         0        0                                         4        200      0         0        0                                                  400      0         0        0                                         5        200      0         100      90                                                 400      0         100      100                                       6        400      0         0        0                                         7        200      0         0        90                                                 400      0         0        0                                         8        200      0         0        0                                                  400      0         0        0                                         9        200      80        0        0                                                  400      70        0        0                                         10       200      0         90       90                                                 200      0         80       100                                                400      0         100      100                                       11       200      0         100      100                                                400      0         100      100                                       12       200      0         0        0                                                  400      0         0        0                                         13       200      60        0        0                                                  400      0         0        0                                         14       200      0         0        50                                                 400      0         0        0                                         15       200      0         0        0                                                  400      0         80       80                                        16       200      80        0        0                                                  400      0         0        0                                         17       200      0         80       80                                                 400      0         60       80                                        18       200      0         30       80                                                 400      0         90       90                                        19       200      0         0        0                                                  400      0         0        0                                         20       200      0         0        0                                                  400      0         0        0                                         21       200      70        100      100                                                400      0         100      60                                        22       200      90        100      100                                                400      0         60       80                                        23       200      0         0        90                                                 400      0         40       80                                        24       400      0         0        0                                         25       200      80        50       60                                                 400      0         0        0                                         26       200      0         100      80                                                 400      0         0        0                                         27       200      0         0        20                                                 400      0         0        0                                         28       200      0         20       30                                                 400      0         0        0                                         29       200      0         100      90                                                 400      0         80       80                                        30       200      0         100      100                                                400      0         100      100                                       31       400      0         0        0                                         32       200      60        100      90                                                 400      0         0        0                                         33       200      0         0        0                                                  400      0         0        0                                         34       200      60        0        0                                                  400      0         0        0                                         35       200      0         0        60                                                 400      0         0        0                                         36       200      0         0        0                                                  400      0         0        0                                         37       200      0         0        0                                                  400      0         0        0                                         38       200      20        0        0                                                  400      20        0        0                                         39       200      0         80       0                                                  400      0         0        0                                         40       200      20        0        0                                                  400      0         0        0                                         41       200      0         100      100                                                400      0         100      100                                       44       200      0         0        0                                                  400      40        0        0                                         45       200      0         0        0                                                  400      0         0        0                                         46       400      0         0        0                                         47       200      0         20       90                                                 400      0         0        0                                         48       200      0         80       60                                                 400      0         0        0                                         49       200      0         0        0                                                  400      0         0        0                                         50       200      0         90       70                                                 400      0         0        0                                         51       200      50        80       80                                                 400      40        0        0                                         52       200      0         0        0                                                  400      0         100      100                                       53       400      0         0        0                                         54       400      0         100      100                                       55       400      0         0        0                                         57       200      0         90       90                                                 400      0         80       100                                       61       400      0         0        N.A.                                      64       400      0         0        0                                         65       200      90        0        0                                                  400      100       0        0                                         67       400      0         0        100                                       68       400      0         0        0                                         72       200      0         0        0                                                  400      0         0        0                                         ______________________________________                                    

Compositions

The compounds of this invention are applied in the form of compositions which are important embodiments of the invention, and which comprise a compound of this invention and a phytologically-acceptable inert carrier. The compositions are either concentrated formulations which are dispersed in water for application, or are dust or granular formulations which are applied without further treatment. The compositions are prepared according to procedures and formulae which are conventional in the agricultural chemical art, but which are novel and important because of the presence therein of the compounds of this invention. Some description of the formulation of the compositions will be given, however, to assure that agricultural chemists can readily prepare any desired composition.

The dispersions in which the compounds are applied are most often aqueous suspensions or emulsions prepared from concentrated formulations of the compounds. Such water-soluble, water-suspendable or emulsifiable formulations are either solids usually known as wettable powders, or liquids usually known as emulsifiable concentrates or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the active compound, an inert carrier and surfactants. The concentration of the active compound is usually from about 10% to about 90% by weight. The inert carrier is usually chosen from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among the sulfonated lignins, the condensed naphthalenesulfonates, the naphthalenesulfonates, the alkylbenzenesulfonates, the alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of the compounds comprise a convenient concentration of a compound, such as from about 50 to about 500 grams per liter of liquid, equivalent to about 10% to about 50%, dissolved in an inert carrier which is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially the xylenes, and the petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are chosen from conventional nonionic surfactants, such as those discussed above.

Aqueous suspensions comprise suspensions of water-insoluble compounds of this invention, dispersed in an aqueous vehicle at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the compound, and vigorously mixing it into a vehicle comprised of water and surfactants chosen from the same types discussed above. Inert ingredients, such as inorganic salts and synthetic or natural gums, may also be added, to increase the density and viscosity of the aqueous vehicle. It is often most effective to grind and mix the compound at the same time by preparing the aqueous mixture, and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.

The compounds may also be applied as granular compositions, which are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the compound, dispersed in an inert carrier which consists entirely or in large part of clay or a similar inexpensive substance. Such compositions are usually prepared by dissolving the compound in a suitable solvent, and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound, and crushing and drying to obtain the desired granular particle size.

Dusts containing the compounds are prepared simply by intimately mixing the compound in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock and the like. Dusts can suitably contain from about 1% to about 10% of the compound.

It is equally practical, when desirable for any reason, to apply the compound in the form of a solution in an appropriate organic solvent, usually a bland petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.

Insecticides and miticides are generally applied in the form of a dispersion of the active ingredient in a liquid carrier. It is conventional to refer to application rates in terms of the concentration of active ingredient in the carrier. The most widely used carrier is water.

The compounds of the invention can also be applied in the form of an aerosol composition. In such compositions the active compound is dissolved or dispersed in an inert carrier, which is a pressure-generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve. Propellant mixtures comprise either low-boiling halocarbons, which may be mixed with organic solvents, or aqueous suspensions pressurized with inert gases or gaseous hydrocarbons.

The actual amount of compound to be applied to loci of insects and mites is not critical and can readily be determined by those skilled in the art in view of the examples above. In general, concentrations of from 10 ppm to 5000 ppm of compound are expected to provide good control. With many of the compounds, concentrations of from 100 to 1500 ppm will suffice. For field crops, such as soybeans and cotton, a suitable application rate for the compounds is about 0.5 to 1.5 lb/A, typically applied in 50 gal/A of spray formulation containing 1200 to 3600 ppm of compound. For citrus crops, a suitable application rate is from about 100 to 1500 gal/A spray formulation, which is a rate of 100 to 1000 ppm.

The locus to which a compound is applied can be any locus inhabited by an insect or arachnid, for example, vegetable crops, fruit and nut trees, grape vines, and ornamental plants. Inasmuch as many mite species are specific to a particular host, the foregoing list of mite species provides exemplification of the wide range of settings in which the present compounds can be used.

Because of the unique ability of mite eggs to resist toxicant action, repeated applications may be desirable to control newly emerged larvae, as is true of other known acaricides.

The following formulations of compounds of the invention are typical of compositions useful in the practice of the present invention.

A. 0.75 Emulsifiable Concentrate

    ______________________________________                                         Compound of Example 25                                                                               9.38%                                                    "TOXIMUL D"           2.50%                                                    (nonionic/anionic surfactant blend)                                            "TOXIMUL H"           2.50%                                                    (nonionic/anionic surfactant blend)                                            "EXXON 200"           85.62%                                                   (naphthalenic solvent)                                                         ______________________________________                                    

B. 1.5 Emulsifiable Concentrate

    ______________________________________                                         Compound of Example 25                                                                             18.50%                                                     "TOXIMUL D"         2.50%                                                      "TOXIMUL H"         2.50%                                                      "EXXON 200"         76.50%                                                     ______________________________________                                    

C. 0.75 Emulsifiable Concentrate

    ______________________________________                                         Compound of Example 41                                                                             9.38%                                                      "TOXIMUL D"         2.50%                                                      "TOXIMUL H"         2.50%                                                      "EXXON 200"         85.62%                                                     ______________________________________                                    

D. 1.0 Emulsifiable Concentrate

    ______________________________________                                         Compound of Example 41                                                                             12.50%                                                     N-methylpyrrolidone 25.00%                                                     "TOXIMUL D"         2.50%                                                      "TOXIMUL H"         2.50%                                                      "EXXON 200"         57.50%                                                     ______________________________________                                    

E. 1.0 Aqueous Suspension

    ______________________________________                                         Compound of Example 25 12.00%                                                  "PLURONIC P-103"       1.50%                                                   (block copolymer of propylene oxide                                            and ethylene oxide, surfactant)                                                "PROXEL GXL"           .05%                                                    (biocide/preservative)                                                         "AF-100"               .20%                                                    (silicon based antifoam agent)                                                 "REAX 88B"             1.00%                                                   (lignosulfonate dispersing agent)                                              propylene glycol       10.00%                                                  veegum                 .75%                                                    xanthan                .25%                                                    water                  74.25%                                                  ______________________________________                                    

F. 1.0 Aqueous Suspension

    ______________________________________                                         Compound of Example 25  12.50%                                                 "MAKON 10" (10 moles ethyleneoxide                                                                     1.00%                                                  nonylphenol surfactant)                                                        "ZEOSYL 200" (silica)   1.00%                                                  "AF-100"                0.20%                                                  "AGRIWET FR" (surfactant)                                                                              3.00%                                                  2% xanthan hydrate      10.00%                                                 water                   72.30%                                                 ______________________________________                                    

G. 1.0 Aqueous Suspension

    ______________________________________                                         Compound of Example 41                                                                               12.50%                                                   "MAKON 10"            1.50%                                                    "ZEOSYL 200" (silica) 1.00%                                                    "AF-100"              0.20%                                                    "POLYFON H"           0.20%                                                    (lignosulfonate dispersing agent)                                              2% xanthan hydrate    10.00%                                                   water                 74.60%                                                   ______________________________________                                    

H. Wettable Powder

    ______________________________________                                         Compound of Example 25                                                                             25.80%                                                     "POLYFON H"         3.50%                                                      "SELLOGEN HR"       5.00%                                                      "STEPANOL ME DRY"   1.00%                                                      gum arabic          0.50%                                                      "HISIL 233"         2.50%                                                      Barden clay         61.70%                                                     ______________________________________                                    

I. Aqueous Suspension

    ______________________________________                                         Compound of Example 25                                                                             12.40%                                                     "TERGITOL 158-7"    5.00%                                                      "ZEOSYL 200"        1.00%                                                      "AF-100"            0.20%                                                      "POLYFON H"         0.50%                                                      2% xanthan solution 10.00%                                                     tap water           70.90%                                                     ______________________________________                                    

J. Emulsifiable Concentrate

    ______________________________________                                         Compound of Example 25                                                                             12.40%                                                     "TOXIMUL D"         2.50%                                                      "TOXIMUL H"         2.50%                                                      "EXXON 200"         82.60%                                                     ______________________________________                                    

K. Wettable Powder

    ______________________________________                                         Compound of Example 41                                                                             25.80%                                                     "SELLOGEN HR"       5.00%                                                      "POLYFON H"         4.00%                                                      "STEPANOL ME DRY"   2.00%                                                      "HISIL 233"         3.00%                                                      Barden clay         60.20%                                                     ______________________________________                                    

L. Emulsifiable Concentrate

    ______________________________________                                         Compound of Example 25                                                                             6.19%                                                      "TOXIMUL H"         3.60%                                                      "TOXIMUL D"         0.40%                                                      "EXXON 200"         89.81%                                                     ______________________________________                                    

M. Wettable Powder

    ______________________________________                                         Compound of Example 25                                                                             25.80%                                                     "SELLOGEN HR"       5.00%                                                      "POLYFON H"         4.00%                                                      "STEPANOL ME DRY"   2.00%                                                      "HISIL 233"         3.00%                                                      Barden clay         60.20%                                                     ______________________________________                                    

N. Aqueous Suspension

    ______________________________________                                         Compound of Example 41                                                                             12.40%                                                     "TERGITOL 158-7"    5.00%                                                      "ZEOSYL 200"        1.00%                                                      "POLYFON H"         0.50%                                                      "AF-100"            0.20%                                                      xanthan solution (2%)                                                                              10.00%                                                     tap water           70.90%                                                     ______________________________________                                     

We claim:
 1. A compound of the formula (1) ##STR12## wherein a) A and D are N and B and E are CR¹ ;b) B and D are N and A and E are CR¹ ; c) E and D are N and A and B are CR¹ ; d) A and E are N and B and D are CR¹ ; e) A and B are N and E and D are CR¹ ; or f) B and E are N and A and D are CR¹ ; where R¹ and R² are independently H, halo, (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, (C₁ -C₄) alkoxy, halo (C₁ -C₄) alkyl, phenyl, or substituted phenyl; X is O, S, SO, SO₂, NR³, or CR⁴ R⁵ where R³ is H, (C₁ -C₄) alkyl, or (C₁ -C₄) acyl, and R⁴ and R⁵ are independently H, (C₁ -C₄) acyl, (C₁ -C₄) alkyl, (C₂ -C₄) alkenyl or alkynyl, CN, or OH, or R⁴ and R⁵ combine to form a carbocyclic ring containing four to six carbon atoms; Y is an alkylene chain 2 to 6 carbon atoms long; Z is a phenyl group of the formula (2) ##STR13## wherein R⁶ to R¹⁰ are independently H, halo, I, (C₁ -C₁₀) alkyl, (C₃ -C₈) alkenyl or -alkynyl, branched (C₃ -C₆) alkyl, alkenyl or alkynyl, (C₃ -C₈) cycloalkyl or cycloalkenyl, halo (C₁ -C₇) alkyl, (C₁ -C₇) alkoxy, (C₁ -C₇) alkylthio, halo (C₁ -C₇) alkoxy, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, phenyl, substituted phenyl, NO₂, acetoxy, OH, CN, SiR¹¹ R¹² R¹³, OSiR¹¹ R¹² R¹³, NR¹⁴ R¹⁵, S(O)R¹⁶, or SO₂ R¹⁷ where R¹¹, R¹², and R¹³ are independently (C₁ -C₄) alkyl, (C₃ -C₄) branched alkyl, phenyl, or substituted phenyl, R¹⁴ and R¹⁵ are independently H, (C₁ -C₄) alkyl, or (C₁ -C₄) acyl, and R¹⁶ and R¹⁷ are (C₁ -C₁₀) alkyl, phenyl, or substituted phenyl, or an acid addition salt of a compound of formula (1).
 2. A compound of claim 1 wherein X is O.
 3. A compound of claim 1 wherein X is NR³.
 4. A compound of claim 3 wherein X is NH.
 5. A compound of claim 1 wherein A and D are N and B and E are CR¹.
 6. A compound of claim 1 wherein at least one of R⁶ to R¹⁰ isbranched (C₃ -C₆) alkyl, halo (C₁ -C₄) alkyl, halo (C₁ -C₄) alkoxy, phenyl, substituted phenyl, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, SiR¹¹ R¹² R¹³, or OSiR¹¹ R¹² R¹³. 